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Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway

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Tumor Biology

Abstract

Berberine has drawn extensive attention toward their wide range of biochemical and pharmacological effects, including antineoplastic effect in recent years, but the precise mechanisms remain unclear. Treatment of human breast cancer cells (MCF-7 and MDA-MB-231 cells) with berberine induced inhibition of cell viability in concentration- and time-dependent manner irrespective of their estrogen receptor (ER) expression. Hoechst33342 staining confirmed berberine induced breast cancer cell apoptosis in time-dependent manner. Because apoptosis induction is considered to be a crucial strategy for cancer prevention and therapy, berberine may be an effective chemotherapeutic agent against breast cancer. To explore the precise mechanism, berberine-induced oxidative stress and mitochondrial-related apoptotic pathway in human breast cancer cells were investigated in this study. In both MCF-7 and MDA-MB-231 cells, berberine increased the production of reactive oxygen species (ROS), which activated the pro-apoptotic JNK signaling. Phosphorylated JNK triggered mitochondria membrane potential (ΔΨm) depolarization and downregulation expression of anti-apoptotic protein Bcl-2 concomitant with the upregulation expression of pro-apoptotic protein Bax. Downregulation of anti-apoptotic Bcl-2 family protein in parallel with loss of ΔΨm, leading to increased the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, and eventually triggered the caspase-dependent and caspase-independent apoptosis. Taken together, our study reveled that berberine exerted an antitumor activity in breast cancer cells by reactive oxygen species generation and mitochondrial-related apoptotic pathway. These finding provide an insight into the potential of berberine for breast cancer therapy.

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Acknowledgments

This work was supported by grants from the Nanjing Medical Science and Technique Development Foundation, Nanjing, Jiangsu, China (Grant No.QYK10156), and the natural science foundation of Jiangsu Province (Grant No.BK20130073). We thank Pro. Sun Y (Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, People’s Republic of China) for providing MCF-7 and MDA-MB-231 breast cancer cell lines.

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Authors and Affiliations

  1. State key Laboratory of Reproductive Medicine, Department of Pharmacy, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, China

    Juan Xie, Yinyan Xu, Xinyan Huang, Yanni Chen, Jing Fu, Mingming Xi & Li Wang

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  1. Juan Xie
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  2. Yinyan Xu
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  3. Xinyan Huang
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  6. Mingming Xi
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  7. Li Wang
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Correspondence to Juan Xie or Li Wang.

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Juan Xie and Yinyan Xu contributed equally to this work.

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Xie, J., Xu, Y., Huang, X. et al. Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway. Tumor Biol. 36, 1279–1288 (2015). https://doi.org/10.1007/s13277-014-2754-7

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  • DOI: https://doi.org/10.1007/s13277-014-2754-7

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